Monoclonal Antibodies in Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (MARALL)

Disease Information

Descriptive Information
Brief Title † Monoclonal Antibodies in Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (MARALL)
Official Title † Phase I/II Study Combining Humanised Anti-CD20 (Veltuzumab), Anti-CD22 (Epratuzumab) and Both Monoclonal Antibodies With Intensive Chemotherapy in Adults With Recurrent or Refractory B-precursor Acute Lymphoblastic Leukaemia (ALL)
Brief Summary The treatment of adult B-cell acute lymphoblastic leukaemia (ALL) has progressed considerably in the past 3 decades, particularly due to intensification of chemotherapies, improved supportive care and the incorporation of stem cell transplantation. However, the maximum tolerability of standard chemotherapeutics has been reached in ALL. Using conventional chemotherapy, 80-85% of adults with ALL will achieve a complete remission (CR). Unfortunately treatment at relapse is generally unsuccessful and rarely results, in long-term survival (7% survival at 5 years). Therefore, the investigators are exploring novel treatment strategies through the use of monoclonal antibodies (MoAbs) directed at surface antigens on leukaemic blasts. Using MoAbs directed against surface proteins on B cells has had excellent results in other B-cell diseases such as low and high grade non-Hodgkin lymphomas, without additional toxicity. There has also been limited evidence from small studies and case reports of the efficacy of MoAbs in ALL. This is a Phase I/II study to determine the safety and tolerability of the combination of veltuzumab and epratuzumab with intensive chemotherapy in patients with relapsed B-cell ALL. A maximum of 51 patients will be treated with a combination of UKALL XII induction chemotherapy and the monoclonal antibodies veltuzumab and epratuzumab. Veltuzumab and epratuzumab are humanised monoclonal antibodies that target CD20 and CD22 surface proteins, respectively. Both of these proteins are expressed on ALL tumour B cells. One group of patients will receive modified UKALL XII chemotherapy + veltuzumab; a second, modified UKALL XII chemotherapy + epratuzumab and if limited toxicity is found in these first 2 groups, a third group will receive, modified UKALL XII chemotherapy + both veltuzumab and epratuzumab. Patients will be assessed for safety, tolerability and disease response. Safety and tolerability will be measured by the number of Dose Limiting Toxicities (DLTs) in each group. Disease response will be measured by the microscopic appearance of patient bone marrow samples at day 29, and by molecular tests for tumour cells in bone marrow.
Detailed Description
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design † Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † The total number of dose limiting toxicity events (DLTs) to measure safety and tolerability
Secondary Outcome Measure † Morphological and molecular remission in bone marrow
Condition † Recurrent or Refractory B Cell Acute Lymphoblastic Leukaemia
Intervention † Biologicalhumanised monoclonal antibody, veltuzumab
Study Arms / Comparison Groups A: Veltuzumab and chemotherapy Veltuzumab and modified UKALL XII chemotherapy B: epratuzumab and chemotherapy epratuzumab and modified UKALL XII chemotherapy C: veltuzumab and epratuzumab and chemotherapy Veltuzumab and Epratuzumab and modified UKALL XII chemotherapy
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Biological
Estimated Enrollment † 55
Start Date † January 2010
Completion Date August 2014
Primary Completion Date August 2014
Eligibility Criteria † Inclusion Criteria: 1. Aged 16 years or over 2. Confirmed diagnosis of recurrent or refractory B-precursor ALL [according to the WHO classification]. 3. Greater than 5% blasts in the bone marrow 4. WHO/ECOG performance status of 0-2 and well enough to receive intensive combination chemotherapy. 5. Negative pregnancy test in women of childbearing potential. Women will not be considered of child bearing potential if they have undergone surgical removal of the uterus or are post menopausal and have been amenorrhoeic for at least 24 months. 6. Patients must have adequate organ function: - Renal function - serum creatinine 50ml/min (measured EDTA or estimated creatinine clearance e.g Cockcroft & Gault) - Liver function (bilirubin/ALT
Gender Both
Ages 16 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † United Kingdom
Administrative Information
NCT ID † NCT01279707
Organization ID 6125
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Queen Mary University of London
Collaborators †† Immunomedics, Inc.
Investigators † Principal Investigator: Matthew Smith, Doctor, Barts and The London NHS Trust
Information Provided By
Verification Date July 2014
First Received Date † April 12, 2010
Last Updated Date July 11, 2014
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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